Some of the Most Important Lab Tests and What They Mean

In many parts of the world, medical providers care for their patients who have HIV/AIDS without the benefit of laboratory tests -- sometimes even the most basic ones. Fortunately, in the United States (and various other countries), medical providers almost always have available to them a wide range of diagnostic tools. Below are some of the most important ones.

Complete Blood Count (CBC)

This tells you whether you are anemic (too few red blood cells), neutropenic (too few of the white blood cells called neutrophils that fight bacterial infections), or thrombocytopenic (too few platelets, or thrombocytes, for your blood to clot normally) -- all of which occur commonly in people with HIV. The CBC also gives you something called the "differential," which is an individual count of all the different kinds of white blood cells: neutrophils, monocytes, lymphocytes, basophils, and eosinophils. It is also crucial in determining your total CD4+ T-cell (or CD4) count, a critical measure of immune function.

CD4 Cell Count

The FACS (not "fax," although pronounced the same way) or Fluorescence Activated Cell Sorter machine identifies CD4 cells and directly measures what their proportion (percent) is of all your lymphocytes (white blood cells) when your blood was drawn. So, the CD4 percent is what the machine actually measures, and the total (or "absolute") CD4 cell count is derived from multiplying the percentage of CD4s by the total lymphocyte count. That is why the differential from the CBC is necessary -- in order to obtain your CD4 cell count.

Over time, the CD4 percent is a more stable measure of your immune system function because the total CD4 count is influenced by your white blood cell count at the moment your blood was drawn, a number that varies constantly. Nonetheless, by habit and tradition, health care providers have used the total CD4 cell count for key decisions, such as when to start HIV meds or preventive therapy for opportunistic infections, like PCP (pneumocystis pneumonia).

This key test tells us how much virus is in a milliliter (abbreviation: mL) of your blood, one-fifth of a teaspoon. Note that it does not tell us how much HIV is in your entire body, where most of the virus is -- in tissues, such as your lymph glands or nodes. Even though this test uses a tiny quantity of blood, it has proven to be a very good indicator of response to antiretroviral therapy.

The most commonly used test is made by Roche, and has established cut-off values for the upper limit of how much virus can be detected and the lower limit, which is referred to as "undetectable" virus, a shorthand way of saying "below the limit of detection." Note that "undetectable" means the amount of HIV is less than the technical ability of the test to detect it and does not mean that HIV is not there. The Ultrasensitive test has a low-end cut-off of less than 20 copies of HIV RNA/mL.

There are other types of viral load tests (see Positively Aware July/August 2011, "Undetectable -- Says Who?"), such as the branched DNA (bDNA) assay, that are sometimes used. There are various technologies, but the measurement principles, with cut-offs for the upper and lower limits, are similar to the RNA PCR tests above.

Serum Chemistries -- Liver and Kidney Function Tests

Liver Function Tests (LFTs): These tests measure some key functions of the liver, a complex organ that performs many important tasks in the body. The liver manufactures proteins that are essential to blood-clotting and to keeping fluid in your bloodstream instead of leaking out into your tissues and causing swelling (edema). The liver breaks down most environmental poisons (toxins) and drugs to rid the body of them. It also forms bile, which is important for digestion.

Amino aspartate transaminase (AST) and alanine aspartate transaminase (ALT) are key enzymes that indicate how well liver cells (hepatocytes) are functioning. The levels of an enzyme called alkaline phosphatase and a protein by-product called bilirubin indicate how well the liver is producing and excreting bile, which is then stored in the gall bladder. Albumin, a protein made in the liver, is critical for keeping fluid in the bloodstream and is an overall measure of nutritional status.

Liver function can be damaged by alcohol abuse, environmental toxins (including street drugs), viral infection of the liver (viral hepatitis), and a long list of diseases and prescription medications. Since people with HIV sometimes also have chronic hepatitis B or C, drink too much, or experience liver damage (hepatotoxicity) from medications, LFTs are important to monitor.

Kidney (renal) function tests: These tests measure how well your kidneys are doing their primary job, which is to rid the body of protein waste (blood urea nitrogen, or BUN) and regulate blood volume by filtering out the waste and extra water to form urine. The two main kidney function tests look at the level of waste as a way to measure how efficiently your kidneys are operating. These tests can provide clues that someone might have HIV-associated nephropathy (HIVAN) or kidney malfunction due to other causes, such as dehydration, diabetes, or drug toxicity.

Since some drugs are excreted from the body by the kidneys, dose adjustments need to be made when a person develops altered kidney function. Awareness of kidney dysfunction is also important when selecting an ARV regimen because some medications, like Viread (tenofovir), are not preferred for someone with underlying kidney disease.

Kidney function should be checked when someone enters HIV care. Thereafter, people at high risk of developing kidney disease (primarily African Americans and diabetics or people with a family history of diabetes) should have their kidney function checked at regular intervals. Routine checks at least annually are also recommended for people on ARV therapy.

Syphilis Blood Test

Syphilis, like HIV, is a sexually transmitted infection that may have no symptoms at all. If left untreated, it can cause -- years later -- significant disease and death due to damage to blood vessels and the brain.

There are a number of blood tests for syphilis (RPR, FTA, syphilis IgG), but the type of test is less important than the fact that everyone with HIV should have one upon entering HIV care; women who become pregnant should also have one to prevent transmission to their unborn baby. After that, screening depends on risk -- people who are at higher risk of exposure through unprotected sex, especially those with multiple partners, may need to be screened regularly. Several outbreaks around the country among men who have sex with men have occurred over the past several years. Sex workers, incarcerated individuals, and people with other sexually transmitted infections are also at high risk. Otherwise, annual re-testing is appropriate.

Tests for Viral Hepatitis

Many HIV-positive people are also infected ("co-infected") with chronic hepatitis B virus (HBV) and/or hepatitis C virus (HCV). It is very important to find this out because, if left untreated, both conditions can ultimately lead to severe scarring of the liver (cirrhosis), liver failure, and liver cancer (hepatocellular carcinoma, or HCC for short).

Some HIV medicines are active against hepatitis B, so it is important to craft an ARV regimen that will adequately treat both HIV and HBV at the same time. Hepatitis C currently requires treatment with two drugs -- peginterferon and ribavirin -- that do not control HIV, and this therapy can be pretty challenging. The use of newly approved drugs for HCV used in addition to the standard combination of peginterferon and ribavirin can markedly improve response to therapy, as well as possibly shortening the treatment period.

In addition to HBV and HCV, it is also important to test blood for proteins that are protective (called antibodies) to hepatitis A (HAV). There is no chronic form of hepatitis A, but if you already have chronic liver disease from hepatitis B and/or C, you can get much sicker from hepatitis A than someone who doesn't have HBV or HCV, because you may already have some liver damage. Since there are vaccines available for hepatitis A and B (but not, unfortunately, for hepatitis C), these should be offered to every HIV-positive person whose blood tests show no immunity to these viruses.

Resistance Tests (Genotype and Phenotype)

These tests tell us whether your virus is resistant to certain HIV drugs (in other words, a given medication will not be effective against your virus). Testing for transmitted resistance is now recommended before starting HIV meds, as up to 12% of people have a virus that is resistant to one or more antiretrovirals. These tests are also used to help choose a new combination of meds for people who are not responding to their current HIV therapy.

Both genotypes and phenotypes are done on a blood sample. Genotypes, which are simpler, faster, and cheaper to perform, identify changes in particular viral genes that are associated with reduced or no response to specific drugs. Phenotypes, which are more complicated, time-consuming, and expensive, test how well your HIV grows in the presence of different concentrations of HIV drugs.

Genotypes may be more than adequate for early resistance because they look at how much resistance the virus has compared to virus with no resistance; phenotypes have some advantages for people with extensive resistance because they can indicate how well the virus responds to various amounts of individual drugs. The phenotype results can be especially useful when there are no "new" drugs available to someone and the only option is a "salvage" regimen of drugs to which the virus is at least partially, if not fully, susceptible.

In the most difficult cases, both tests add information of value. Cost can limit the availability of these tests, especially the phenotype.

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